par Kaufman, Marcelle 
;Andris, Fabienne ;Leo, Oberdan
Référence Proceedings of the National Academy of Sciences of the United States of America, 96, 7, page (3894-3899)
Publication Publié, 1999-03
;Andris, Fabienne ;Leo, Oberdan Référence Proceedings of the National Academy of Sciences of the United States of America, 96, 7, page (3894-3899)
Publication Publié, 1999-03
Article révisé par les pairs
| Résumé : | Interaction of the antigen-specific receptor of T lymphocytes with its antigenic ligand can lead either to cell activation or to a state of profound unresponsiveness (anergy). Although subtle changes in the nature of the ligand or of the antigen-presenting cell have been shown to affect the outcome of T cell receptor ligation, the mechanism by which the same receptor can induce alternative cellular responses is not completely understood. A model for explaining both positive (cell proliferation and cytokine production) and negative (anergy induction) signaling of T lymphocytes is described herein. This model relies on the autophosphorylative properties of the tyrosine kinases associated with the T cell receptor. One of its basic assumptions is that the kinase activity of these receptor-associated enzymes remains above background level after ligand removal and is responsible for cellular unresponsiveness. Using a simple Boolean formalism, we show how the timing of the binding and intracellular signal-transduction events can affect the properties of receptor signaling and determine the type of cellular response. The present approach integrates into a common framework a large body of experimental observations and allows specification of conditions leading to cellular activation or to anergy. |
